Skip to main content
SpringerLink
Log in

Enhanced nimodipine bioavailability after oral administration of nimodipine with morin, a flavonoid, in rabbits

  • Articles
  • Drug Development
  • Published:
Archives of Pharmacal Research Aims and scope Submit manuscript

Abstract

The aim of this study was to investigate the effect of morin on the bioavailability of nimodipine after administering nimodipine (15 mg/kg) orally to rabbits either co-administered or pretreated with morin (2, 10 and 20 mg/kg). The plasma concentrations of nimodipine in the rabbits pretreated with morin were increased significantly (p<0.05 at 10 mg/kg, p<0.01 at 20 mg/kg) compared with the control, but the plasma concentrations of nimodipine co-administered with morin were not significant. The areas under the plasma concentration-time curve (AUC) and the peak concentrations (Cmax) of the nimodipine in the rabbits pretreated with morin were significantly higher (p<0.05 at 10 mg/kg, p<0.01 at 20 mg/kg), but only the Cmax of nimodipine co-administered with morin 10 mg/kg was increased significantly (p<0.05). The absolute bioavailability (A.B%) of nimodipine in the rabbits pretreated with morin was significantly (p<0.05 at 10 mg/kg, p<0.01 at 20 mg/kg) higher (54.1–65.0%) than the control (36.7%). The increased bio-availability of nimodipine in the rabbits pretreated with morin might have been resulted from the morin, which inhibits the efflux pump P-glycoprotein and the first-pass metabolizing enzyme by cytochrome P-450 3A4 (CYP 3A4).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Choi, H. J. and Choi, J. S., Effects of morin pretreatment on the pharmacokinetics of diltiazem and its major metabolite, desacetyldiltiazem in rats.Arch. Pharm. Res., 28, 970–976 (2005a).

    Article  PubMed  CAS  Google Scholar 

  • Choi, J. S. and Han, H. K., Pharmacokinetic interaction between diltiazem and morin, a flavonoid, in rats.Pharmacol. Res., 52, 386–391 (2005b).

    Article  PubMed  CAS  Google Scholar 

  • Dixon, R. A., and Steele, C. L., Flavonoids and isoflavonoids—a gold mine for metabolic engineering.Trends Plant Sci., 4, 394–400 (1999).

    Article  PubMed  Google Scholar 

  • Epstein, M. and Loutzenhister, R. D., Effects of calcium antagonists on renal hemodynamics,Am. J. Kidney Dis., 16, 10–14 (1990).

    PubMed  CAS  Google Scholar 

  • Fang, S. H., Hou, Y. C., Chang, W. C., Hsiu, S. L., Chao, P. D. L., and Chiang, B. L., Morin sulfates glucuronides exert anti-inflammatory activity on activated macrophages and decreased the incidence of septic shock.Life Sci. 74, 743–756 (2003).

    Article  PubMed  CAS  Google Scholar 

  • Francis, A. R., Shetty, T. K., and Bhattacharya, R. K., Modulating effect of plant flavonoids on the mutagenicity of N-methyl-N-nitro-N-nitrosoguanidine.Carcinogenesis, 10, 1953–1955 (1989).

    Article  PubMed  CAS  Google Scholar 

  • Gan, L. L., Moseley, M. A., Khosla, B., Augustijns, P. F., Bradshaw, T. P., Hendren, R. W., and Thakker, D. R., CYP3A-Like cytochrome P450-mediated metabolism and polarized efflux of cyclosporin A in Caco-2 cells: interaction between the two biochemical barriers to intestinal transport.Drug Metab. Dispos., 24, 344–349 (1996).

    PubMed  CAS  Google Scholar 

  • Gottesman, M. M. and Pastan, I., Biochemistry of multidrug resistance mediated by the multidrug transporter.Annu. Rev. Biochem., 62, 385–427 (1993).

    Article  PubMed  CAS  Google Scholar 

  • Guengerich, F. P., Brian, W. R., Iwasaki, M., Sari, M. A., Baarnhielm, C., and Berntssom, P., Oxidation of dihydropyridine calcium channel blockers and analogues by human liver cytochrom P-450 3A4,J. Med. Chem., 34, 1834–1844 (1991).

    Article  Google Scholar 

  • Hanasaki, Y., Ogawa, S., and Fukui, S., The correlation between active oxygens scavenging and antioxidative effects of flavonoids.Free Radic. Biol. Med. 16, 845–850 (1994).

    Article  PubMed  CAS  Google Scholar 

  • Hodek, P., Trefil, P., and Stiborova, M., Flavonoids-potent and versatile biologically active compounds interacting with cytochromes P450.Chem. Biol. Interact., 139, 1–21 (2002).

    Article  PubMed  CAS  Google Scholar 

  • Hsiu, S. L., Hou, Y. C., Wang, Y. H., Tsao, C. W., Su, S. F., and Chao, P. D., Quercetin significantly decreased cyclosporin oral bioavailability in pigs and rats.Life Sci., 72, 227–235 (2002).

    Article  PubMed  CAS  Google Scholar 

  • Ito, K., Kusuhara, H., and Sugiyama, Y., Effects of intestinal CYP3A4 and P-glycoprotein on oral drug absorption theoretical approach.Pharm. Res., 16, 225–231 (1999).

    Article  PubMed  CAS  Google Scholar 

  • Kazda, S., Garthoff, B., Krause, H. P., and Schlossmann, K., Cerebrovascular effects of the calcium antagonistic dihydropyridine derivative nimodipine in animal experiments,Arzneimittelforschung., 32, 331–338 (1982).

    PubMed  CAS  Google Scholar 

  • Maruhn, D., Siefert, H. M., Weber, H., Ramsch, K., and Suwelack, D., Pharmacokinetics of nimodipine. communication: absorption, concentration in plasma and excretion after single administration of nimodipine in rat, dog and monkey,Arzneimittelforschung., 35, 1781–1786 (1985).

    PubMed  CAS  Google Scholar 

  • Nguyen, H., Zhang, S., and Morris, M. E., Effect of flavonoids on MRP1-mediated transport in Panc-1 cells.J. Pharm. Sci., 92, 250–257 (2003).

    Article  PubMed  CAS  Google Scholar 

  • Qian, M., and Gallo, J. M., High-perfomance liquod chromatographic determinination of the calcium channel blocker nimodipine in monkey plasma,J. Chromatogr., 578, 316–320 (1992).

    Article  PubMed  CAS  Google Scholar 

  • Ramsch, K. D., Ahr, G., Tettenborn, D., and Auer, L. M., Overview on pharmacokinetics of nimodipine in healthy volunteer and in patients with subarachnoid hemorrhage,Neurochirurgia., 28, 74078 (1985).

    Google Scholar 

  • Rocci, M. L. and Jusko, W. J., LAGRAN program for area and moments in pharmacokinetic analysis,Computer Programs in Biomedicine, 16, 203–209 (1983).

    Article  PubMed  Google Scholar 

  • Saeki, T., Ueda, K., Tanigawara, Y., Hori, R., and Komano, T., P-glycoprotein-mediated transcellular transport of MDR-reversing agents.FEBS Lett., 324, 99–102 (1993).

    Article  PubMed  CAS  Google Scholar 

  • Scherling, D., Buhner, K., Krause, H. P., Karl, W., and Wunsche, C., Biotransformation of nimodipine in rat, dog and monkey,Arzneimittelforschung., 41, 392–398 (1991).

    PubMed  CAS  Google Scholar 

  • Scholz, H., Pharmacological aspects of calcium channel blockers.Cardiovasc. Drugs Ther., 10, 869–872 (1997).

    Article  PubMed  Google Scholar 

  • Suwelack, D., Weber, H., and Maruhn, D., Pharmacokinetics of nimodipine, communication: absorption, concentration in plasma and excretion after single administration of [14C] nimodipine in rat, dog and monkey,Arzneimittelforschung., 35, 1787–1794 (1985).

    PubMed  CAS  Google Scholar 

  • Wacher, V. H., Silverman, J. A., Zhang, Y., and Benet, L. Z., Role of P-glycoprotein and cytochrome P450 3A in limiting oral absorption of peptides and peptidomimetics.J. Pharm. Sci., 87, 1322–1330 (1998).

    Article  PubMed  CAS  Google Scholar 

  • Wacher, V. J., Salphati, L., and Benet, L. Z., Active secretion and enterocytic drug metabolism barriers to drug absorption.Adv. Drug Deliv. Rev., 46, 89–102 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Watkins, P. B., The barrier function of CYP3A4 and P-glycoprotein in the small bowel.Adv. Drug Deliv. Rev., 27, 161–170 (1996).

    Article  Google Scholar 

  • Zhang, S. and Morris, M. E., Effects of the flavonoids biochanin A, morin, phloretin, and silymarin on P-glycoprotein-mediated transport.J. Pharmacol. Exp. Ther., 304, 1258–1267 (2003).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. College of Pharmacy, Chosun University, 501-759, Gwangju, Korea

    Jun Shik Choi

  2. Chosun Nursing College, 280, Seosuk-Dong, Dong-Gu, 501-825, Gwangju, Korea

    Jin Pil Burm

Authors
  1. Jun Shik Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jin Pil Burm
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jin Pil Burm.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Choi, J.S., Burm, J.P. Enhanced nimodipine bioavailability after oral administration of nimodipine with morin, a flavonoid, in rabbits. Arch Pharm Res 29, 333–338 (2006). https://doi.org/10.1007/BF02968580

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02968580

Key words

Search

Navigation